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Biomedical subjects

M Cummins

Publications and source records attributed to M Cummins.

17 recordsLinked to original sources

Detection of proliferating cell nuclear antigen in paraffin-embedded specimens is dependent on preembedding tissue handling and fixation.

Immunohistochemical detection of proliferating cell nuclear antigen (PCNA), a cell cycle-related protein used to estimate tumor growth fraction, is variable in formalin-fixed compared with methanol-fixed tissue specimens. This is assumed to result from conformational changes in the antigenic epitope induced by formaldehyde; therefore, to be susceptible to retrieval in archival specimens. In this study, formalin fixation reduced the intensity of staining and the number of positive cells to approximately 25% of those in methanol-fixed material. The washing of tissue specimens prior to methacarn fixation also reduced PCNA staining. Loss of staining was not restored after use of a commercial retrieval kit recommended for PCNA immunohistochemistry. Immunoblotting of formalin fixatives and saline washings after removal of tissue specimens consistently demonstrated the presence of PCNA-like activity in solution. We conclude that the exceptional solubility of PCNA is responsible for reduced immunostaining in formalin-fixed material, that the loss is irreversible, and that methanol or methacarn is the fixative of choice for PCNA immunohistochemistry.

Animals

Obstructive sialadenitis: a rat model.

Obstructive adenitis of major salivary glands is a common entity. Although the pathologic features are well recognized, the various cell types involved in the atrophy and subsequent regeneration of the obstructed salivary gland have been controversial. For this reason, an animal model of obstructive sialadenitis that induced atrophy in the rat parotid gland was developed. A clamp was devised that would occlude the main excretory duct of the gland inducing atrophy, but that, following removal, left the duct patent and allowed regeneration to occur. Both atrophy and regeneration were studied, and the results presented. The number and location of cycling acinar, intercalated, striated, and excretory duct cells were identified, using an antibody to proliferating cell nuclear antigen (PCNA). All cell types were induced to cycle during both the atrophy and regeneration phase, but the degree of cycling was more pronounced during regeneration. Three days after release of the duct obstruction, cycling acinar cells had increased 40-fold, while striated and intercalated ducts increased 6.5- and 5.0-fold, respectively. More importantly, peak cycling of acinar cells preceded, but paralleled, the increase in acinar cell composition of the gland. This model of obstructive sialadenitis indicates that all cell types are responsible for regeneration in the obstructed rat parotid gland.

Animals

Alternate, adjacent 2 and 3:1 meiotic segregation products from a balanced t(13;18) (q12;q11) carrier.

We present a case in which alternate, adjacent 2 and 3:1 meiotic segregations have occurred in the pregnancies of a female carrier of a balanced reciprocal translocation -46,XX,t(13;18) (q12;q11). Products of five conceptions effectively showed trisomy 18q, trisomy 18p or monosomy 18p. This is one of the rare rearrangements which can give rise to a variety of segregation modes including adjacent 2.

Chromosomes, Human, Pair 13

A small one-band paracentric inversion inv (4) (p15.3p16.3).

A neonate with aniridia was found to have a one band paracentric inversion of the short arm of chromosome 4. This was initially difficult to interpret on high resolution banding. The inversion was present in three generations of the family.

Aniridia

Job sharing.

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Female

The causes of low oestrogen excretion in pregnancy: the development of diagnostic methods for the antenatal detection of familial congenital adrenocortical hypoplasia.

A pregnancy producing a boy with congeital adrenocortical hypoplasia is described. Consistently low oestrogen excretion, less than 10 umol/24 h, was not associated with any anatomical abnormality or diminished growth of the fetus as judged by ultrasound examination. Fetoplacental steroid sulphatase definciency was excluded by finding normal maternal excretion of oestrogen precursors, the 3Beta-hydroxy-5-ene steroid sulphates. Generalized adrenocortical hypoplasia was proven in the baby boy by analysis of steroid netabolites excreted in his urine. He suffered from salt loss and progressive jaundice. Both were responsive to gluco- and mineralo-corticoid replacement therapy. It is suggested that amniocentesis may be required for the antenatal diagnosis of congenital adrenocortical hypoplasia.

Adrenal Cortex Hormones

Follow-up of children of diabetic mothers.

The results of a follow-up study of infants of diabetic mothers are presented. The antenatal care of all such mothers was supervised in a combined clinic by obstetricians and physicians, and good diabetic control was achieved in most of them. 51 mothers delivered 73 infants, all liveborn, between the years 1964 and 1972 inclusive at Hammersmith Hospital. There were no fetal deaths. 66 infants survived the neonatal period, and 63 the first 2 years of life. 51 children, including all those seriously ill in the neonatal period, could be traced. Detailed neurological and general examinations including skinfold measurements were made, and the IQ measured. Four children were found to have major handicaps. These were severe deafness, epilepsy, low IQ, and myopia. No other neurological abnormalities were detected, and the distribution of full-scale IQs was normal. The distribution of height and head circumference centiles was near normal, but an increased number of children had weights above the 90th centile. No significant congenital malformations were found in these 51 survivors, and none has so far developed diabetes.

Adolescent

Infants of very low birthweight. A 15-year analysis.

357 babies weighing 501--1500 g were born alive at Hammersmith Hospital in 1961--75. 58.5% died in the neonatal period and 1.4% at 4--25 months of age. 1.4% of the total are untraced, 5.3% have major handicap, 5.6% have minor handicap, and 27.8% are apparently normal. There was no significant improvement in neonatal mortality in three 5-year periods, 1961--65, 1966--70, and 1971--75, except that more small-for-gestational-age babies survived in the last period than in the first. More of these babies survived than did babies whose birthweight was appropriate for gestational age. There was no significant improvement in the proportion of handicapped children among the very-low-weight liveborn babies throughout the 15-year period, despite increasing complexity of care.

Adolescent

Vertical transmission of hepatitis B surface antigen in carrier mothers in two west London hospitals.

126 children of 102 hepatitis B surface antigen (HBsAg) carrier mothers were delivered at Hammersmith Hospital and Queen Charlotte's Maternity Hospital, between 1971 and mid-1978. Blood tests on 110 of these children showed that 8 out of the 18 with Chinese mothers, but only 6 out of the 92 other children, have become HBsAg positive. The presence of maternal hepatitis B e antigen (HBeAg) is also significantly correlated with transmission of HBsAg to the children. The management of children whose mothers are carriers is discussed.

Carrier State

Cytohormonal patterns in mature and pre-term babies.

Comparison of cytohormonal patterns in full-term and pre-term babies of both sexes showed significant differences. At birth, irrespective of gestational age, both groups had high oestrogen levels, reflecting the maternal hormonal environment, but whereas the mature neonates were capable of metabolising and excreting the excess hormone within the first week of life, the pre-term infants took much longer to do so. It is thought that immaturity or impairment of liver function is at least partially responsible for this finding.

Cell Count

Simplified management of pregnancy complicated by diabetes.

Simple methods for the management of pregnancy complicated by diabetes are described. Emphasis was placed on keeping patients out of hospital, good control of diabetes and vaginal delivery at 38 weeks: using these methods, there were nine perinatal deaths in a consecutive series of 101 pregnancies complicated by diabetes. Four of the perinatal deaths were due to the respiratory distress syndrome. The patients whose diabetes was diagnosed during pregnancy had significantly heavier babies (18 pregnancies, mean birth weight 3337 g) than the established diabetics (83 pregnancies, mean weight 3011 g) despite significantly lower fasting blood glucose levels in the former and similar mean gestational ages at delivery. Mean fasting blood glucose levels for the whole series during the first, second and third trimesters were 9.0, 6.7 and 5.6 mmol/l respectively. The mean duration of antenatal stay in hospital for complications related to diabetes was 29 days. Diabetic retinopathy did not seem to be adversely affected by pregnancy.

Birth Weight

Hepatitis B antigen-positive obstetric patients.

In a period of six years (1971--77) 9400 sera taken at booking from antenatal patients were examined for hepatitis B antigen (HBsAg), and 40 patients were positive. These 40 patients had 45 pregnancies and were treated with special precautions so far as venepuncture and the management of delivery were concerned. No member of the hospital staff dealing with the patients developed hepatitis B. All infants born to these mothers were normal, two infants were HBsAg-positive at 7 months and 2 years, but are clinically well. No obstetric problems attributable to the HBsAg-positive state were encountered.

Adolescent

The relationship between overdrive suppression and overdrive excitation in ventricular pacemakers in dogs.

We studied the excitatory and inhibitory effects of overdrive on idioventricular pacemakers in anesthetized dogs with recently induced complete atrioventricular block. The following results were obtained: (1) a slow driving rate may induce a temporary rhythm which may be reinstituted with additional stimuli; (2) the induced rhythm may appear as coupled extrasystoles which, on interruption of the drive, are found to be self-sustaining; (3) during continued slow driving, extrasystoles may appear and disappear in a cyclical manner; (4) a short period of fast driving may be followed by a fast new rhythm, the rate and duration of which are a function of the rate and duration of drive; (5) fast driving may induce a new rhythm at a rate below predrive control; (6) after a long period fast driving, only suppression follows; and (7) intermittent periods of fast driving lead to a summation of inhibition with each successive period. These results suggest the following conclusions: (1) under certain conditions, electrical driving instead of inducing suppression may induce a rhythm ("overdrive excitation") at a rate similar to, faster then, or slower ("inhibited excitation") than control; (2) the duration of diastole and the number of driven beats are major factors in the induction of new rhythms; and (3) overdrive excitation is counteracted by overdrive inhibition, with development of the former requiring fewer beats than the latter.

Animals